Exam 4 Mfm Genetics Of Cancer

Front 1

Genetic Basis of Cancer:

somatic and/or inherited germline mutations in
1)proto-oncogenes
2)tumor suppressor genes
3)DNA mismatch repair genes

susceptibility genes (...), environmental factors (...), and viruses

Back 1

polymorphisms
teratogens

Front 2

oncogenic = ...

Back 2

tumor forming

Front 3

Oncogenic Viruses:

Papilloma (HPV)
Epstein-Barr (EBV)
Hepatitis B (HBV)

*study of the genetics and replicative processes of oncogenic retroviruses has revealed some of the key cellular processes involved in ... (formation of cancer

Back 3

carcinogenesis

Front 4

...: normal genes that play key roles in cell growth and differentiation

...: mutated proto-oncogene that has cancer-forming properties

...: viral gene that has oncogenic properties

Back 4

proto-oncogenes
cellular oncogene (c-onc)
viral oncogene (v-onc)

Front 5

Functions of Oncogenes:

...
v-SIS, HST, INT-2

Growth factor ...
ERB-2, KIT, MET
...
ras, RAF

... proteins
FOS, JUN, ERB-A

... regulators
MYC, bcl-2

Back 5

Growth factors
receptors
Signal transduction
DNA-binding
Cell cycle

Front 6

Amplification of Oncogenes:

gene amplification or ... of proto-oncogenes can convert them into ...

common examples: MYC, ERB-B2, cyclin D1 in some ... cancers

Back 6

over-expression
oncogenes
breast

Front 7

which disease is this?

unusual lymphoma of jaw found in children in Africa

90% affected have translocation of the c-MYC oncogene, such that it is amplified/overexpressed by an immunoglobulin promoter region

Back 7

Burkitt Lymphoma

Front 8

which disease is this?

Philadelphia chromosome found in blood and bone marrow cells

involves translocation between chromosomes 9 and 22 = t(9;22)

results in a chimeric oncogene with transforming activity in blood cells

Back 8

Chronic Myeloid Leukemia

Front 9

Tumor Suppressor Genes

first thought of as “anti-...”

could suppress malignant phenotype in hybrid cancer cell lines

function is to ... inappropriate cell proliferation

may become ... or an oncogene may ... the function of tumor-suppressor proteins

results in loss of function

Back 9

oncogenes
suppress
mutated
inactivate

Front 10

if you mutate a oncogene, it leads to a ...

if you mutate a tumor suppressor gene, leads to a ...

Back 10

gain of function

loss of function

Front 11

What disease is this?

rare, highly malignant childhood cancer of the retina (before age of 5)

non-hereditary and hereditary forms

mutation in RB1 tumor suppressor gene

also may carry risk of developing other malignancies later in life

Back 11

Retinoblastoma (RB)

Front 12

what is this?

Emerged from Rb studies

Hereditary form: due to initial germline mutation in RB1 gene, but also must have an additional somatic mutation to inactivate the second RB1 allele

Non-hereditary form: must have two independent inactivating somatic mutations to RB1 locus

Back 12

Two-Hit Hypothesis

Front 13

which form of the 2 hit hypothesis is this?
-bilaterally, multifocal, younger age.

What about this?
-unilateral, unifocus, older age of onset

Back 13

hereditary form
non-hereditary form

Front 14

Loss of ....

-common occurrance in cancers
-explains 2-hit hypothesis
-mutant allele will be expressed
-loss of normal allele

Back 14

heterozygosity

Front 15

Tp53:

tumor suppressor gene that encodes p53

... of the genome”

most ... mutated of all the known cancer genes

... syndrome

Back 15

“guardian
frequently
Li-Fraumeni

Front 16

... silences/inactivates genes
-X-inactivation
-genomic imprinting

... can lead to loss of imprinting (LOI) and activation of oncogenes.

... can lead to inactivation of tumor suppressor genes.

Back 16

DNA methylation
Hypomethylation
Hypermethylation

Front 17

... = shows the link between cancer formation and age. Reason for this is because telomeres get shorter, which leads to chromosome becoming less stable.

Back 17

Telomere crisis

Front 18

Genetics of Common Cancers (the "big 3")

... cancer
1 in 40 persons in Western societies will develop colon cancer.

... cancer
1 in 12 women in Western societies will develop breast cancer.

... cancer
the most common cancer overall after breast cancer, and the most common cancer affecting men

Back 18

Colorectal
Breast
Prostate

Front 19

which cancer is this?

majority develop from benign adenomas

long 5-10 year transition from a small adenomatous polyp to an invasive cancer

involves accumulations of genetic alterations (Tp53, RAS, LOH)

Back 19

colorectal cancer

Front 20

Forms of Colorectal Cancer:

... Adenomatous Polyposis (FAP)
-APC gene (adenomatous polyposis coli)

... in Colorectal Cancer
-DCC gene (deleted in colorectal cancer)

... Non-Polyposis Colorectal Cancer (HNPCC)
-Mut mismatch repair genes

Back 20

Familial
Deleted
Hereditary

Front 21

which cancer is this?

multiple genetic alterations involved:
-erb-B, myc, int-2 oncogenes
-BRCA1 and BRCA2 tumor suppressor genes
-LOH
-EMSY amplification

Back 21

breast cancer

Front 22

which cancer is this?

Genetic alterations:
-LOH
-HPC1 and HPC2 (hereditary prostate cancer)
-BRCA1 and BRCA2

Back 22

prostate cancer